Natural products from reconstructed bacterial genomes of the Middle and Upper Paleolithic.

Major advances over the past decade in the field of ancient DNA are providing access to past paleogenomic diversity, but the diverse functions and biosynthetic capabilities of this growing paleome remain largely elusive. We investigated the dental calculus of 12 Neanderthals and 52 anatomically modern humans ranging from 100,000 years ago to the present and reconstructed 459 bacterial metagenome-assembled genomes. We identified a biosynthetic gene cluster shared by seven Middle and Upper Paleolithic individuals that allows for the heterologous production of a class of previously unknown metabolites that we name "paleofurans." This paleobiotechnological approach demonstrates that viable biosynthetic machinery can be produced from the preserved genetic material of ancient organisms, allowing access to natural products from the Pleistocene and providing a promising area for natural product exploration.

The arrival of millets to the Atlantic coast of northern Iberia.

Despite being one of the most important crops in the recent prehistory of Eurasia, the arrival and exploitation of millets in the westernmost part of Europe are still largely underexplored. Here and for the first time, we report multipronged biomolecular evidence of millet consumption along the Atlantic façade of northern Iberia through a combination of radiocarbon dating, stable isotopes, and dental calculus analyses on the human individuals found in the burial site of El Espinoso cave (Asturias, Spain). The high-resolution chronological framework established for individuals placed the burials between 1235 and 1099 cal. BC. The discovery of high δ13C values on their bone collagen and the identification of polyhedral starch grains within their dental plaque underline the relevance of C4 plants in their diet and highlights the timing of the systematic consumption of millets in the Late Bronze Age. Our data support previous regional archaeobotanical evidence and establish a more precise chronology of the dispersal of millets into northern Iberia during the Bronze Age, becoming an essential crop until the arrival of maize from America after AD 1492. This study emphasizes the importance of multidisciplinary methods to ascertain the origin and development of agricultural practices during recent prehistory.

Human forager response to abrupt climate change at 8.2 ka on the Atlantic coast of Europe.

The cooling and drying associated with the so-called '8.2 ka event' have long been hypothesized as having sweeping implications for human societies in the Early Holocene, including some of the last Mesolithic hunter-gatherers in Atlantic Europe. Nevertheless, detailed 'on-site' records with which the impacts of broader climate changes on human-relevant environments can be explored have been lacking. Here, we reconstruct sea surface temperatures (SST) from δ18O values measured on subfossil topshells Phorcus lineatus exploited by the Mesolithic human groups that lived at El Mazo cave (N Spain) between 9 and 7.4 ka. Bayesian modelling of 65 radiocarbon dates, in combination with this δ18O data, provide a high-resolution seasonal record of SST, revealing that colder SST during the 8.2 ka event led to changes in the availability of different shellfish species. Intensification in the exploitation of molluscs by humans indicates demographic growth in these Atlantic coastal settings which acted as refugia during this cold event.

Temporal and spatial variability of prehistoric aquatic resource procurement: a case study from Mesolithic Northern Iberia.

Prehistoric shell middens hold valuable evidence of past human-environment interactions. In this study, we used carbon (δ13C) and oxygen (δ18O) stable isotopes of Mytilus galloprovincialis shells excavated from El Perro, La Fragua and La Chora, three Mesolithic middens in Cantabria, Northern Spain, to examine hunter-gatherer subsistence strategies in terms of seasonality and collection areas. Furthermore, we used shell δ18O to reconstruct water temperature during the early Holocene. Stable isotopes reveal a shellfish harvesting diversification trend represented by the gradual establishment of the upper estuaries as new procurement areas and an increase of harvesting mobility in both coastal and in-land sites. These innovations in subsistence strategies during the Mesolithic coincided with major changes in the surrounding environment as attested by the water temperature reconstructions based on δ18O and backed by several global and regional records. Overall, our results show that shell δ13C and δ18O stable isotopes have an underexplored potential as provenance proxies which stimulates their application to the archaeological record to further understand prehistoric human resource procurement and diet.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

Correction: Chronological reassessment of the Middle to Upper Paleolithic transition and Early Upper Paleolithic cultures in Cantabrian Spain.

[This corrects the article DOI: 10.1371/journal.pone.0194708.].

Chronological reassessment of the Middle to Upper Paleolithic transition and Early Upper Paleolithic cultures in Cantabrian Spain.

Methodological advances in dating the Middle to Upper Paleolithic transition provide a better understanding of the replacement of local Neanderthal populations by Anatomically Modern Humans. Today we know that this replacement was not a single, pan-European event, but rather it took place at different times in different regions. Thus, local conditions could have played a role. Iberia represents a significant macro-region to study this process. Northern Atlantic Spain contains evidence of both Mousterian and Early Upper Paleolithic occupations, although most of them are not properly dated, thus hindering the chances of an adequate interpretation. Here we present 46 new radiocarbon dates conducted using ultrafiltration pre-treatment method of anthropogenically manipulated bones from 13 sites in the Cantabrian region containing Mousterian, Aurignacian and Gravettian levels, of which 30 are considered relevant. These dates, alongside previously reported ones, were integrated into a Bayesian age model to reconstruct an absolute timescale for the transitional period. According to it, the Mousterian disappeared in the region by 47.9-45.1ka cal BP, while the Châtelperronian lasted between 42.6k and 41.5ka cal BP. The Mousterian and Châtelperronian did not overlap, indicating that the latter might be either intrusive or an offshoot of the Mousterian. The new chronology also suggests that the Aurignacian appears between 43.3-40.5ka cal BP overlapping with the Châtelperronian, and ended around 34.6-33.1ka cal BP, after the Gravettian had already been established in the region. This evidence indicates that Neanderthals and AMH co-existed <1,000 years, with the caveat that no diagnostic human remains have been found with the latest Mousterian, Châtelperronian or earliest Aurignacian in Cantabrian Spain.

Automated Measurement of Magnesium/Calcium Ratios in Gastropod Shells Using Laser-Induced Breakdown Spectroscopy for Paleoclimatic Applications.

The chemical composition of mollusk shells offers information about environmental conditions present during the lifespan of the organism. Shells found in geological deposits and in many archeological sites can help to reconstruct past climatic conditions. For example, a correlation has been found between seawater temperature and the amount of some substituent elements (e.g., magnesium, strontium) in the biogenerated calcium carbonate matrix of the shell, although it is very species-specific. Here we propose the use laser-induced breakdown spectroscopy (LIBS) to estimate Mg/Ca ratios in modern specimens of the common limpet Patella vulgata. An automated setup was used to obtain a sequence of Mg/Ca ratios across a sampling path that could be compared with the seawater temperatures recorded during the organism's lifespan. Results using four shells collected in different months of the year showed a direct relationship between the Mg/Ca ratios and the seawater temperature, although the sequences also revealed small-scale (short-term) variability and an irregular growth rate. Nevertheless, it was possible to infer the season of capture and the minimum and maximum seawater temperatures from the LIBS sequences. This fact, along with the reduction in sampling and measurement time compared with other spectrometric techniques (such as inductively coupled plasma mass spectrometry [ICP-MS]), makes LIBS useful in paleoclimatic studies.

Late-glacial recolonization and phylogeography of European red deer (Cervus elaphus L.).

The Pleistocene was an epoch of extreme climatic and environmental changes. How individual species responded to the repeated cycles of warm and cold stages is a major topic of debate. For the European fauna and flora, an expansion-contraction model has been suggested, whereby temperate species were restricted to southern refugia during glacial times and expanded northwards during interglacials, including the present interglacial (Holocene). Here, we test this model on the red deer (Cervus elaphus) a large and highly mobile herbivore, using both modern and ancient mitochondrial DNA from the entire European range of the species over the last c. 40,000 years. Our results indicate that this species was sensitive to the effects of climate change. Prior to the Last Glacial Maximum (LGM) haplogroups restricted today to South-East Europe and Western Asia reached as far west as the UK. During the LGM, red deer was mainly restricted to southern refugia, in Iberia, the Balkans and possibly in Italy and South-Western Asia. At the end of the LGM, red deer expanded from the Iberian refugium, to Central and Northern Europe, including the UK, Belgium, Scandinavia, Germany, Poland and Belarus. Ancient DNA data cannot rule out refugial survival of red deer in North-West Europe through the LGM. Had such deer survived, though, they were replaced by deer migrating from Iberia at the end of the glacial. The Balkans served as a separate LGM refugium and were probably connected to Western Asia with genetic exchange between the two areas.

Prescripción racional de benzodiacepinas en adultos mayores en la atención primaria de salud / Rational Prescription of Benzodiazepines in Elderly in Primary Care

Para evaluar el consumo de medicamentos del grupo de las benzodiacepinas por la población, especialmente los adultos mayores en la atención primaria de salud, se realizó un estudio descriptivo transversal de tipo prescripción-indicación en la Farmacia Principal No 2 del municipio Holguín, en el trimestre comprendido entre enero-marzo de 2007, con el objetivo de identificar el uso de estos fármacos en una muestra de 239 pacientes. Con la información obtenida se confeccionó una base de datos, los cuales se procesaron de forma automatizada, mediante las técnicas descriptivas para variables discretas, los resultados se expresan en porcentaje y en tablas. La prescripción de benzodiacepinas predominó en las edades comprendidas entre 60-74 años y en el sexo femenino. La ansiedad es la principal indicación de benzodiacepinas y el nitrazepam el fármaco más indicado. Se evaluó como irracional e excesiva la prescripción de todos los fármacos estudiados...(AU)

A descriptive and cross-sectional study was carried out aimed at assessing the consumption of benzodiazepines in elderly in primary care from January to March 2007. The sample was constituted by 239 patients. A data base was done which were processed through descriptive techniques for discreet variables. The results were expressed in percentage and tables. Benzodiacepines prescription prevailed in the age group between 60-74 years as well as the female sex. Benzodiacepines were used mainly for anxiety and nitrazepam was the most useful drug. The prescription of all drugs was considered irrational and excessive...(AU)

La prescripción de benzodiacepinas en el adulto mayor, un problema médico social actual / Benzodiazepines Prescription in Elderly, a Current Socio- Medical Problem

Se realizó un estudio de revisión con el objetivo de evaluar el uso de benzodiacepinas en el adulto mayor. Fue evidente que la prescripción de las mismas constituye un problema médico - social debido a su uso irracional y excesivo, por lo que se hace necesario ejecutar acciones que contribuyan al uso correcto de medicamentos para mejorar la calidad de vida del paciente geriátrico, así como disminuir los costos en nuestros servicios de salud. Se incluyó una propuesta de estrategia sustentada en tres objetivos incorporar y sostener los conocimientos relacionados con la farmacología geriátrica, promocionar el uso racional de medicamentos, así como ejecutar el control sobre los prescriptores...(AU)

A review study aimed at assessing the use of benzodiazepines in elderly was carried out. The prescriptions constituted a socio-medical problem due to the excessive irrational use of this medication. Therefore different actions were developed in order to use this medication correctly to improve the elderly`s quality of life. A set of strategies was included based on three objectives including and maintaining the knowledge regarding geriatric pharmacology; promoting the rational use of medications as well as to control the medication prescribing...(AU)

Prescripción adecuada de fármacos en el adulto mayor / Appropriate Drugs Prescription in Elderly

Aparejado al envejecimiento poblacional se incrementa el consumo de fármacos en la población La terapéutica farmacológica de los ancianos continúa planteando importantes dificultades la principal es la indefinición del sujeto al existir una diversidad de características que condicionan que se dé una variabilidad individual Esto impide generalizar conceptos y dificulta la extrapolación de los datos obtenidos en grupos de población reducidos y concretos En el presente trabajo de revisión se exponen algunos aspectos farmacogerontológicos para lograr una adecuada prescripción en el adulto mayor...(AU)

Together with the population aging the drugs consumption are increased There are difficulties related with pharmacological therapy in elderly The main difficulty is the one which is close related with different characteristics of the individuals Therefore is very difficult for specialists to prescribe medication according to elderly characteristics In this review article some pharmaco gerontologic aspects were discussed to achieve an appropriate prescription in elderly...(AU)

La medicina basada en la evidencia como parte del razonamiento científico actual / The medicine base on of evidence

La medicina basada en la evidencia (MBE) se basa principalmente en la aplicación del método epidemiológico al método experimental, esta ha constituído un avance en el desarrollo del conocimiento médico, el cual ha permitido el surgimiento de la Farmacoepidemiología como nueva rama de la farmacología cuyo objetivo es lograr un uso más racional de los medicamentos. La MBE goza de gran prestigio en la actualidad, aunque no esta exenta de críticas, abarca númerosas especialidades de la medicina occidental y tradicional(AU)